Neuropediatrics 2017; 48(06): 467-472
DOI: 10.1055/s-0037-1603976
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Intractable Epilepsy due to MTR Deficiency: Importance of Homocysteine Analysis

Jonna Komulainen-Ebrahim1, 2, 3, 4, Eemeli Saastamoinen2, 5, Elisa Rahikkala1, 2, 6, Heli Helander1, 3, Reetta Hinttala1, 2, 4, Leila Risteli2, 7, 8, Heikki Rantala1, 2, 3, Johanna Uusimaa1, 2, 3, 4
  • 1PEDEGO Research Unit (Research Unit for Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology and Ophthalmology), University of Oulu, Oulu, Finland
  • 2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
  • 3Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
  • 4Biocenter Oulu, University of Oulu, Oulu, Finland
  • 5Research Unit of Clinical Neuroscience, Department of Neurology, University of Oulu, Oulu, Finland
  • 6Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland
  • 7Northern Finland Laboratory Centre NordLab, Oulu, Finland
  • 8Department of Clinical Chemistry, University of Oulu, Oulu, Finland
Further Information

Publication History

16 January 2017

16 May 2017

Publication Date:
30 June 2017 (eFirst)


Background Methionine synthase deficiency is a rare inborn error of intracellular cobalamin metabolism caused by mutations in the MTR (5-methyltetrahydrofolate-homocysteine S-methyltransferase) gene, resulting in megaloblastic anemia and neurologic symptoms.

Methods and Results We describe for the first time a homozygous MTR gene c.3518C > T (p.P1173L) mutation in a patient with severe megaloblastic anemia, developmental delay, and drug-resistant seizures associated with hyperhomocysteinemia and hypomethioninemia. Methionine synthase activity was only 9% of the reference value, and MTR protein expression was decreased in the fibroblasts of the patient. The clinical features of our patient are similar to previously published patients with the complementation type G disorder of methionine synthase deficiency with the exception of drug-resistant seizures. However, intramuscular injections of hydroxocobalamin (OHCbl) in conjunction with betaine and folic acid provided verified clinical and electrophysiological treatment response.

Conclusion This study emphasizes the importance of early diagnosis of patients having neurologic symptoms due to methionine synthase deficiency where early treatment has significant effects on the clinical outcome of the patients. Elevated level of plasma homocysteine together with low methionine in plasma amino acid analysis should raise a suspicion of remethylation disorder.


This work was supported by grants from the Research Council for Health of the Academy of Finland (JU, Decision number 138566; RH, Decision number 266498 and 273790), the Foundation for Pediatric Research, Special State Grants for Health Research in the Department of Pediatrics and Adolescence at Oulu University Hospital, Oulu, Finland, The Alma and K. A. Snellman Foundation, Oulu, Finland, and Finnish Cultural Foundation, North Ostrobothnia Regional Fund.